Telaprevir | VX-950 | CAS#402957-28-2

MedKoo Cat#: 315233 | Name: Telaprevir

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Telaprevir (VX-950), marketed under the brand names Incivek and Incivo, is a pharmaceutical drug for the treatment of hepatitis C co-developed by Vertex Pharmaceuticals and Johnson & Johnson. It is a member of a class of antiviral drugs known as protease inhibitors. Specifically, telaprevir inhibits the hepatitis C viral enzyme NS3.4A serine protease. Telaprevir is only indicated for use against hepatitis C genotype 1 viral infections and has not been proven to have an effect on or being safe when used for other genotypes of the virus. The standard therapy of pegylated interferon and ribavirin is less effective on genotype 1.

Chemical Structure

Telaprevir

CAS#402957-28-2

Theoretical Analysis

MedKoo Cat#: 315233

Name: Telaprevir

CAS#: 402957-28-2

Chemical Formula: C36H53N7O6

Exact Mass: 679.4057

Molecular Weight: 679.85

Elemental Analysis: C, 63.60; H, 7.86; N, 14.42; O, 14.12

Price and Availability

Size	Price	Availability
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,250.00	Ready to ship
1g	USD 1,950.00	Ready to ship
2g	USD 2,950.00	Ready to ship
5g	USD 4,950.00	Ready to ship
10g	USD 8,950.00	Ready to ship

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Synonym

VX950; VX950; VX 950; Incivek; Incivo; Telaprevir;

IUPAC/Chemical Name

(3S,3aS,6aR)-2-[(2S)-2-[[(2S)-2-cyclohexyl-2-(pyrazine-2-carbonylamino)acetyl]amino]-3,3-dimethylbutanoyl]-N-[(3S)-1-(cyclopropylamino)-1,2-dioxohexan-3-yl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-3-carboxamide

InChi Key

BBAWEDCPNXPBQM-GDEBMMAJSA-N

InChi Code

InChI=1S/C36H53N7O6/c1-5-10-25(29(44)34(48)39-23-15-16-23)40-33(47)28-24-14-9-13-22(24)20-43(28)35(49)30(36(2,3)4)42-32(46)27(21-11-7-6-8-12-21)41-31(45)26-19-37-17-18-38-26/h17-19,21-25,27-28,30H,5-16,20H2,1-4H3,(H,39,48)(H,40,47)(H,41,45)(H,42,46)/t22-,24-,25-,27-,28-,30+/m0/s1

SMILES Code

O=C([C@@H]1[C@](CCC2)([H])[C@]2([H])CN1C([C@@H](NC([C@H](C3CCCCC3)NC(C4=NC=CN=C4)=O)=O)C(C)(C)C)=O)N[C@@H](CCC)C(C(NC5CC5)=O)=O

Appearance

solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO (50mg/mL).

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C20R05B18

QC Data

View QC data: current batch, Lot#C20R05B18

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Telaprevir (VX-950) is a highly selective, reversible, and potent peptidomimetic that inhibits SARS-CoV-2 3CLpro activity as well as HCV NS3-4A protease; the steady-state inhibitory constant (Ki) of Telaprevir is 7 nM against a genotype 1 (H strain) NS3 protease domain plus a NS4A cofactor peptide.

In vitro activity:

The anti-HCV activity of VX-950 (Fig.1) was examined in Con1 (genotype 1b) subgenomic HCV replicon cells. In this system, inhibition of HCV NS3-4A protease by VX-950 was expected to block viral polyprotein processing and subsequently decrease viral RNA replication and total HCV RNA levels in the replicon cells. As shown in Fig.2, VX-950 reduced HCV RNA levels in a time- and dose-dependent manner. The IC50s following a 24-, 48-, 72-, and 120-h incubation with VX-950 were determined to be 0.574, 0.488, 0.210, and 0.139 μM, respectively, indicating an increase in inhibitory effects with time. These results show that the IC50 declined as the culture time increased. Following three independent experiments using the 48-h incubation in the presence of 2% FBS, the average (±standard deviation [SD]) IC50 of VX-950 was determined to be 0.354 ± 0.035 μM, and the average (±SD) IC90 was 0.830 ± 0.190 μM. After a 48-h incubation with VX-950, no significant cytotoxicity, as evaluated in an MTS-based cell viability assay, was observed in the replicon cells. The average CC50 (±SD) of VX-950 in HCV replicon cells was 83 ± 27 μM, which resulted in a selective index, i.e., the n-fold value of CC50 over IC50, of 230 ± 59. In both parental Huh-7 and HepG2 cell lines, no significant cytotoxicity was observed after a 48-h incubation with up to 30 μM VX-950 in the presence of DMEM plus 2% FBS. Reference: Antimicrob Agents Chemother. 2006 May; 50(5): 1813–1822. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1472227/

In vivo activity:

The ability of VX-950 to inhibit HCV protease-dependent cleavage and subsequent secretion of SEAP from the liver into the blood was tested in mice. Five groups of 6-week-old SCID mice (6 animals per group) were injected with 109 IFU per mouse of recombinant adenovirus Ad-WT-HCVpro-SEAP through the tail vein. Each group of mice was given two oral administrations of VX950 at one of the following doses: 10, 25, 75, 150, or 300 mg/kg. As shown in Fig.6B, there was an ∼5-fold reduction of serum SEAP activity in mice dosed with VX-950 at either 10 or 25 mg/kg, which had an average value (±SEM) of 18.7 ± 8.3% or 18.4 ± 5.4%, respectively, compared to those administered vehicle (100 ± 28%). These data demonstrated that VX-950 was able to inhibit the HCV NS3-4A serine protease activity in mouse liver and block cleavage and subsequent secretion of SEAP into blood circulation in these mice. As shown in Fig.6C, there was a dose-dependent increase in VX-950 exposure at 1 h postdosing in both liver and plasma. At the lowest dose tested (10 mg/kg), the level of VX-950 in the mouse liver 1 h after oral dosing was 3.86 ± 0.18 μg/g. Assuming the density of liver to be 1 g/ml, this liver concentration of VX-950 at 1 h corresponded to 5.68 ± 0.27 μM, which was about sixfold higher than that in the plasma (0.94 ± 0.09 μM). This liver concentration at 1 h is about 16-fold higher than the 48-h IC50 of VX-950 (354 nM) in HCV replicon cells. At doses higher than 10 mg/kg, the ratio of liver-to-plasma exposure of VX-950 1 h after dosing ranged from 11- to 16-fold. In mice and rats, VX-950 achieved excellent exposure in the liver, which is the primary organ of HCV infection, suggesting that adequate exposures of the drug in humans can be achieved. Reference: Antimicrob Agents Chemother. 2006 Mar; 50(3): 899–909. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1426435/

	Solvent	mg/mL	mM
Solubility
	DMSO	64.0	94.14

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 679.85 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Jiang M, Mani N, Lin C, Ardzinski A, Nelson M, Reagan D, Bartels D, Zhou Y, Nicolas O, Rao BG, Müh U, Hanzelka B, Tigges A, Rijnbrand R, Kieffer TL. In vitro phenotypic characterization of hepatitis C virus NS3 protease variants observed in clinical studies of telaprevir. Antimicrob Agents Chemother. 2013 Dec;57(12):6236-45. doi: 10.1128/AAC.01578-13. Epub 2013 Oct 7. PMID: 24100495; PMCID: PMC3837892. 2. Lin K, Perni RB, Kwong AD, Lin C. VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCv replicon cells. Antimicrob Agents Chemother. 2006 May;50(5):1813-22. doi: 10.1128/AAC.50.5.1813-1822.2006. PMID: 16641454; PMCID: PMC1472227. 3. Perni RB, Almquist SJ, Byrn RA, Chandorkar G, Chaturvedi PR, Courtney LF, Decker CJ, Dinehart K, Gates CA, Harbeson SL, Heiser A, Kalkeri G, Kolaczkowski E, Lin K, Luong YP, Rao BG, Taylor WP, Thomson JA, Tung RD, Wei Y, Kwong AD, Lin C. Preclinical profile of VX-950, a potent, selective, and orally bioavailable inhibitor of hepatitis C virus NS3-4A serine protease. Antimicrob Agents Chemother. 2006 Mar;50(3):899-909. doi: 10.1128/AAC.50.3.899-909.2006. PMID: 16495249; PMCID: PMC1426435.

In vitro protocol:

In vivo protocol:

1. Perni RB, Almquist SJ, Byrn RA, Chandorkar G, Chaturvedi PR, Courtney LF, Decker CJ, Dinehart K, Gates CA, Harbeson SL, Heiser A, Kalkeri G, Kolaczkowski E, Lin K, Luong YP, Rao BG, Taylor WP, Thomson JA, Tung RD, Wei Y, Kwong AD, Lin C. Preclinical profile of VX-950, a potent, selective, and orally bioavailable inhibitor of hepatitis C virus NS3-4A serine protease. Antimicrob Agents Chemother. 2006 Mar;50(3):899-909. doi: 10.1128/AAC.50.3.899-909.2006. PMID: 16495249; PMCID: PMC1426435.

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PMID: 37835845; PMCID: PMC10572573. 5: Samantaray M, Pattabiraman R, Murthy TPK, Ramaswamy A, Murahari M, Krishna S, Kumar SB. Structure-based virtual screening of natural compounds against wild and mutant (R1155K, A1156T and D1168A) NS3-4A protease of Hepatitis C virus. J Biomol Struct Dyn. 2024 Oct;42(16):8505-8522. doi: 10.1080/07391102.2023.2246583. Epub 2023 Aug 30. PMID: 37646701. 6: Zhang YY, Peng JJ, Chen D, Liu HQ, Yao BF, Peng J, Luo XJ. Telaprevir Improves Memory and Cognition in Mice Suffering Ischemic Stroke via Targeting MALT1-Mediated Calcium Overload and Necroptosis. ACS Chem Neurosci. 2023 Sep 6;14(17):3113-3124. doi: 10.1021/acschemneuro.3c00250. Epub 2023 Aug 9. PMID: 37559405. 7: Basile G, Vetere A, Hu J, Ijaduola O, Zhang Y, Liu KC, Eltony AM, De Jesus DF, Fukuda K, Doherty G, Leech CA, Chepurny OG, Holz GG, Yun SH, Andersson O, Choudhary A, Wagner BK, Kulkarni RN. 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Adoption of new therapies in the treatment of Hepatitis: a verification of the accuracy of budget impact analysis to guide investment decisions. Expert Rev Pharmacoecon Outcomes Res. 2022 Sep;22(6):927-939. doi: 10.1080/14737167.2022.2057950. Epub 2022 Apr 4. PMID: 35320682.